Dataset Information

The role of ^mSEPT9 in screening, diagnosis, and recurrence monitoring of colorectal cancer.

ABSTRACT:

Background

The application of circulating, cell-free, methylated Septin9 (^mSEPT9) DNA in screening and recurrence monitoring is highly promising. CpG island methylator phenotype (CIMP) is associated with microsatellite instability (MSI). The present study was performed to determine the diagnostic accuracy of ^mSEPT9 for colorectal cancer (CRC) and to evaluate its utility in CRC screening and recurrence monitoring.

Methods

For screening and diagnosis of CRC, peripheral ^mSEPT9 detection and fecal occult blood test (FOBT) were performed in 650 subjects, then the level of CEA, CA19-9 and CA724 was quantified in 173 subjects. Clinicopathological parameters and mismatch repair protein were detected among subjects with CRC. For recurrence monitoring of CRC, the sensitivity of ^mSEPT9 of 70 subjects was compared with tumor markers and contrast enhanced computed tomography (CECT).

Results

Seventy-three percent of CRC patients were ^mSEPT9-positive at 94.5% specificity, and 17.1% of patients with intestinal polyps and adenoma were ^mSEPT9-positive at 94.5% specificity, which were higher than FOBT for the screening of CRC. The sensitivity and specificity of ^mSEPT9 for diagnosis and recurrence monitoring were higher than that of CEA, CA19-9 and CA724. The combined detection of ^mSEPT9 and CECT enhanced the sensitivity for recurrence monitoring. Pre-therapeutic levels of ^mSEPT9 were strongly associated with TNM stage, Dukes stages and mismatch repair deficiency (dMMR).

Conclusions

^mSEPT9 analysis might be popularized as a routine biomarker for CRC screening. The combined detection of ^mSEPT9 and CECT can play an important role for recurrence monitoring. CIMP was highly associated with the pathological stage of CRC and dMMR.

SUBMITTER: Sun J

PROVIDER: S-EPMC6518628 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

The role of <sup>m</sup>SEPT9 in screening, diagnosis, and recurrence monitoring of colorectal cancer.

Sun Jie J Fei Fei F Zhang Mingqing M Li Yuwei Y Zhang Xipeng X Zhu Siwei S Zhang Shiwu S

BMC cancer 20190514 1

<h4>Background</h4>The application of circulating, cell-free, methylated Septin9 (<sup>m</sup>SEPT9) DNA in screening and recurrence monitoring is highly promising. CpG island methylator phenotype (CIMP) is associated with microsatellite instability (MSI). The present study was performed to determine the diagnostic accuracy of <sup>m</sup>SEPT9 for colorectal cancer (CRC) and to evaluate its utility in CRC screening and recurrence monitoring.<h4>Methods</h4>For screening and diagnosis of CRC, pe ...[more]

PMID: 31088406

Similar Datasets

Project description:BackgroundColorectal cancer (CRC) screening can help to reduce its incidence and mortality. Noninvasive strategies, such as plasma analysis of epigenetic alterations, can constitute important biomarkers of CRC detection.ObjectiveThis study aimed to evaluate the plasma methylation status of SEPT9 and BMP3 promoters as biomarkers for detection of CRC and its precursor lesions in a Brazilian population.MethodsPlasma samples from 262 participants of the CRC screening program of Barretos Cancer Hospital who had a positive fecal occult blood test and underwent colonoscopy and cancer patients were analyzed. Participants were grouped according to the worst lesion detected in the colonoscopy. Cell-free circulating DNA (cfDNA) was bisulfite treated followed by the analysis of SEPT9 and BMP3 methylation status using a droplet digital PCR system (ddPCR). The best methylation cutoff value for group discrimination was calculated by receiver operating characteristic (ROC) curve analysis.ResultsAmong the 262 participants, 38 were diagnosed with CRC, 46 with advanced adenomas 119 with nonadvanced adenomas, three with sessile serrated lesions, and 13 with hyperplastic polyps. In 43 participants, no lesion was detected in the colonoscopy and were used as controls. The CRC group showed the highest cfDNA concentration (10.4 ng/mL). For the SEPT9 gene, a cutoff of 2.5% (AUC = 0.681) that discriminates between CRC and the control group resulted in CRC sensitivity and specificity of 50% and 90%, respectively. Concerning the BMP3 gene, a cutoff of 2.3% (AUC = 0.576) showed 40% and 90% of sensitivity and specificity for CRC detection, respectively. Combining SEPT9, BMP3 status, and age over 60 years resulted in a better performance for detecting CRC (AUC = 0.845) than the individual gene models, yielding 80% and 81% of sensitivity and specificity, respectively.ConclusionThe present study suggests that a combination of SEPT9 and BMP3 plasma methylation, along with age over 60 years, showed the highest performance in detecting CRC in a Brazilian population. These noninvasive biomarkers can potentially serve as useful tools for CRC screening programs.

Project description:BackgroundAn unhealthy lifestyle is associated with the risk of colorectal cancer (CRC), but it is unclear whether overall lifestyle after a CRC diagnosis is associated with risks of recurrence and mortality.ObjectivesTo examine associations between postdiagnosis lifestyle and changes in lifestyle after a CRC diagnosis with risks of CRC recurrence and all-cause mortality.MethodsThe study population included 1425 newly diagnosed, stage I-III CRC patients from 2 prospective cohort studies enrolled between 2010 and 2016. Lifestyle, including BMI, physical activity, diet, and alcohol intake, was assessed at diagnosis and at 6 months postdiagnosis. We assigned lifestyle scores based on concordance with 2 sets of cancer prevention guidelines-from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) and the American Cancer Society (ACS)-and national disease prevention guidelines. Higher scores indicate healthier lifestyles. We computed adjusted HRs and 95% CIs using Cox regression.ResultsWe observed 164 recurrences during a 2.8-year median follow-up and 171 deaths during a 4.4-year median follow-up. No associations were observed for CRC recurrence. A lifestyle more consistent with the ACS recommendations was associated with a lower all-cause mortality risk (HR per +1 SD, 0.85; 95% CI: 0.73-0.995). The same tendency was observed for higher WCRF/AICR (HR, 0.92; 95% CI: 0.78-1.08) and national (HR, 0.90; 95% CI: 0.77-1.05) lifestyle scores, although these associations were statistically nonsignificant. Generally, no statistically significant associations were observed for BMI, physical activity, diet, or alcohol. Improving one's lifestyle after diagnosis (+1 SD) was associated with a lower all-cause mortality risk for the ACS (HR, 0.80; 95% CI: 0.67-0.96) and national (HR, 0.84; 95% CI: 0.70-0.999) scores, yet was statistically nonsignificant for the WCRF/AICR score (HR, 0.94; 95% CI: 0.78-1.13).ConclusionsA healthy lifestyle after CRC diagnosis and improvements therein were not associated with the risk of CRC recurrence, but were associated with a decreased all-cause mortality risk.

Dataset Information

The role of ^mSEPT9 in screening, diagnosis, and recurrence monitoring of colorectal cancer.

Background

Methods

Results

Conclusions

Publications

The role of <sup>m</sup>SEPT9 in screening, diagnosis, and recurrence monitoring of colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

The role of mSEPT9 in screening, diagnosis, and recurrence monitoring of colorectal cancer.

Background

Methods

Results

Conclusions

Publications

The role of <sup>m</sup>SEPT9 in screening, diagnosis, and recurrence monitoring of colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

The role of ^mSEPT9 in screening, diagnosis, and recurrence monitoring of colorectal cancer.